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Introduction: Although current guidelines recommend against routine antibiotic prescription for acute exacerbation of bronchial asthma, children with acute exacerbation of asthma receive antibiotic treatment more frequently. In addition, those antibiotics are often prescribed only for exacerbation of asthma without concurrent bacterial infection. Objective: To clarify the association between antibiotic treatment and bacterial colonization in acute exacerbation of asthma, we investigated whether or not antibiotics affect the clinical condition, laboratory findings, and pharyngeal bacterial colonization in those patients. Methods: Potential bacterial pathogens were investigated in pharyngeal samples of 111 children with acute exacerbation of asthma (mean/median age: 2.8/2.6 years old, respectively). We collected clinical data, such as the duration of wheezing and antibiotic use, and measured the peripheral white blood cell counts, C-reactive protein, and serum levels of total and allergen-specific IgE. Results: Antibiotics were used in 50.5% patients with acute asthma exacerbation and included cephalosporin, penicillin, macrolide, and others. Episodes of wheezing were significantly longer in patients with antibiotic treatment than in those without it (6.7 ± 3.6 days vs. 6.0 ± 3.1, p = 0.044). Similarly, episodes of wheezing were significantly longer in moderate exacerbation patients with antibiotics than in those without them. Furthermore, in patients with Streptococcus pneumoniae, antibiotic treatment was associated with an extended duration of wheezing in cases of acute moderate exacerbation (7.0 ± 2.4 days vs. 4.8 ± 4.1, p = 0.043). Conclusions: These results suggest that antibiotic treatment in acute exacerbation of asthma might lead to longer asthmatic symptoms, specifically in patients with pharyngeal S. pneumoniae colonization.

Cytogenetic abnormalities are a major risk factor for relapse after hematopoietic stem cell transplantation (HSCT) for myelodysplastic syndrome (MDS). We aimed to evaluate the value of the five-group cytogenetic classification according to the revised International Prognostic Scoring System (R-IPSS) for predicting the outcome after HSCT in pediatric patients with MDS. We retrospectively analyzed the Japanese registration data of 242 pediatric patients with MDS. According to the R-IPSS classification, 112 (45.5%) patients had good, 55 (22.7%) had intermediate, 64 (26.4%) had poor, and 11 (4.6%) had very poor cytogenetics. The 5-year overall survival (5yOS) was 72%, 69%, 59%, and 30% in the good, intermediate, poor, and very poor cytogenetic subgroups (p = 0.026), respectively. The very good, good, and intermediate subgroups were grouped into a "standard" subgroup and reclassified into three subgroups (standard, poor, and very poor). Patients with very poor risk had worse 5yOS (hazard ratio 2.17, 95% confidence interval (CI) 1.02-4.61; p = 0.04) and a much higher 5yCIR (hazard ratio 2.52, 95% CI 1.05-6.04; p = 0.04) than those of patients in the standard group in the multivariate analysis, indicating that very poor risk cytogenetic characteristics independently predicted worse outcome after HSCT in pediatric patients with MDS.

PurposeHematopoietic cell transplantation (HCT) is a curative therapy for most patients with inborn errors of immunity (IEI). We conducted a nationwide study on HCT for patients with IEI other than severe combined immunodeficiency (non-SCID) in Japan.MethodsData from the Japanese national database (Transplant Registry Unified Management Program, TRUMP) for 567 patients with non-SCID IEI, who underwent their first HCT between 1985­ and 2016, were retrospectively analyzed.ResultsThe 10-year overall survival (OS) and event-free survival (EFS) was 74% and 64%, respectively. The 10-year OS for HCT from unrelated bone marrow (URBM), accounting for 39% of HCTs, was comparable to that for HCT from matched-sibling donor (MSD), being 79% and 81%, respectively. HCT from unrelated cord blood (URCB), accounting for 27% of HCTs, was also common, with a 10-year OS of 69% but less robust engraftment. The intensity of conditioning was not associated with OS, hematologic recovery, or retransplantation incidence. Multivariate analyses of data on those receiving HCT during the 2006–2016 period revealed that respiratory impairment at HCT was associated with poor OS (hazard ratio [HR], 2.3; P = 0.01) and that URCB (HR, 2.7; P = 0.003) and related donor other than MSD (HR, 2.7; P = 0.02) were associated with poor EFS.ConclusionsWe present the 1985–2016 status of HCT for non-SCID IEI in Japan with sufficient statistical power, highlighting the potential of URBM as an alternative donor and the substantial applicability of URCB. Detailed evaluation is needed for optimizing the HCT strategy for each IEI.

Background/Aim: Here, we investigated whether bortezomib as a maintenance therapy affected outcomes in transplant-ineligible patients with multiple myeloma (MM). Patients and Methods: Following induction therapy with bortezomib, maintenance therapy with bortezomib (1.3 mg/m2) and dexamethasone (20 mg) was administered once or twice every 4 weeks until disease progression. The endpoints of this study were time to next treatment and overall survival. Results: Seventy-six newly diagnosed, transplant-ineligible patients were treated with a bortezomib-based regimen; 28 discontinued induction therapy, 27 did not receive maintenance therapy after induction therapy (the non-maintenance group), and 21 did (the maintenance group). In the three groups, the median times to the next required treatment were 3, 14, and 37 months, respectively. The 3-year overall survival rates were 55%, 69%, and 85%, respectively. There were no significant differences in patient characteristics between the non-maintenance and maintenance groups, except for poorer estimated glomerular filtration rates in the maintenance group. Conclusion: Bortezomib maintenance therapy may be a useful option for transplant-ineligible patients with MM.

Mucopolysaccharidosis type IH (MPS IH, Hurler syndrome) is a progressive, multisystem autosomal recessive lysosomal storage disorder resulting in the consequent accumulation of glycosaminoglycans. It is well recognized that early hematopoietic stem cell transplantation (HSCT) prevents neurocognitive decline in MPS IH. We followed the divergent clinical course in two Japanese siblings with MPS IH. The elder sister (proband) received a diagnosis of MPS IH at 6 months old. At the time of this diagnosis enzyme replacement therapy (ERT) was not available in Japan. She developed severe and recurrent respiratory disease and died at 1 year 10 months of age. Her younger sister also received a diagnosis of MPS IH, but at 18 days of age, and started ERT at 34 days of age. ERT continued until 8 months of age and prevented the progression of somatic manifestations of MPS IH. She received HSCT at 9 months old. Five years after HSCT she had no symptoms of MPS IH except for mild signs of dysostosis multiplex and mild cardiac valvular disease. Her neurological function was generally preserved compared with her elder sister. The prognosis and quality of life differed significantly between the sisters. Therefore, early HSCT can preserve neurocognition by preventing the neurodegeneration from MPS IH. In addition, ERT initiated during the asymptomatic period prevented the patient from developing somatic manifestations and enabled successful HSCT in this case.

A step-economical method for synthesis of α-CF2H-substituted ketones from readily available alkene feedstocks has been developed. Radical difluoromethylation of aromatic alkenes combining DMSO oxid...

Monofluoromethyl (CH2F) radical can be easily generated from a sulfoximine-based precursor (CH2F–S(=O)(=NTs)-Ph) by the action of visible-light metal-free photoredox catalysis with readily accessib...

Recently, photoinduced radical difluoromethylation has emerged as a step-economical synthetic method of CHF2-containing compounds. In this article, difluoromethylation of alkenes, isonitriles and aryl bromides promoted by photoredox catalysis is described together with a non-catalytic photoinduced system. Representative reactions will be discussed for each highlighted difluoromethylating reagent. In addition, related monofluoromethylation with their corresponding monofluoromethylating reagents is also discussed.

The recording performance of a new prototype magnetic tape based on perpendicularly oriented strontium ferrite particles is investigated using a 29 nm wide tunneling magnetoresistive reader. At a linear density of 702 kbpi, a post-detection byte-error rate of 2.8e-2 is demonstrated based on measured recording data and a software read channel. The read channel uses a 64-state implementation of an extended version of a data-dependent noise-predictive maximum-likelihood detection scheme that tracks the first and second order statistics of the data-dependent noise. At the demonstrated post-detection byte-error rate, a post-error-correction-coding byte-error rate of less than 1e-20 can be achieved using an iterative decoding architecture. To facilitate aggressive track-density scaling, we made multiple advances in the area of track following. First, we developed a new timing-based servo pattern and implemented a novel quad channel averaging scheme. Second, we developed a new field programmable gate array prototyping platform to enable the implementation of quad channel averaging. Third, we enhanced our low disturbance tape transport with a pair of 20 mm diameter air bearing tape guides and a prototype track-following actuator. Fourth, we developed a novel low friction tape head and finally, we designed a set of tape speed optimized track-following controllers using the model-based H∞ design framework. Combining these technologies, we achieved a position error signal (PES) characterized by a standard deviation ≤ 3.18 nm over a tape speed range of 1.2 to 4.1 m/s. This magnitude of PES in combination with a 29 nm wide reader enables reliable recording at a track width of 56.2 nm corresponding to a track density of 451.9 ktpi, for an equivalent areal density of 317.3 Gb/in2.

The risk factors for bleomycin-induced lung injury (BLI), a fatal complication of cancer chemotherapy, are not well-established. The renin-angiotensin-aldosterone system (RAAS) has recently been suggested to play a role in the development of lung injury. This study clarified the impact of hypertension (HTN) and the administration of RAAS inhibitors on BLI occurrence in patients treated with bleomycin-containing regimens.We retrospectively analyzed the data of 190 patients treated with a bleomycin-containing regimen for Hodgkin lymphoma or germ cell tumors at our institutions from 2004 to 2018.Overall, 190 patients received bleomycin, and symptomatic BLI occurred in 21 (11.1%) cases. In the multivariate analysis, age ≥ 65 years (odd ratio, 10.90; 95% confidence interval, 3.72-32.20; P .001) and history of HTN (odds ratio, 3.32; 95% confidence interval, 1.07-10.30; P = .04) were found to be significant risk factors for BLI onset. BLI occurred in 3.6% (n = 5) of patients with no risk, 11.8% (n = 2) of those whose only risk factor was HTN, 31.6% (n = 6) of those whose only risk factor was age ≥ 65 years, and 57.1% (n = 8) of those with both risk factors (P .001). BLI-induced mortality rates in each group were 0.0% (n = 0), 5.9% (n = 1), 10.5% (n = 2), and 42.9% (n = 6) (P .001), respectively. Among 31 patients with HTN, BLI incidence was 12.5% in patients who were administered RAAS inhibitors and 53.3% in those who were not (P = .02).Older age and history of HTN were independent risk factors for the development of BLI, and the administration of RAAS inhibitors might reduce the onset of BLI.

Nodal marginal zone lymphoma (NMZL) is a form of nodal B-cell lymphoma exhibiting proliferation of abnormal lymphocytes at the circumference of the mantle zone in the lymph nodes. Although the outcome of patients with this disease is often favorable, we recently encountered a patient with a CD5-positive NMZL who was resistant to chemotherapy. A 67-year-old woman complaining of systemic lymph node swelling was referred to our hospital. After biopsy of the neck lymph node, she was diagnosed with CD5-positive NMZL. Disease progression was revealed after 16 months, and she was initially treated with chemotherapy consisting of rituximab, cyclophosphamide, vincristine, and prednisolone (R-CVP). However, this therapy was ineffective. Subsequent therapy with rituximab and bendamustine also failed to induce remission. A rebiopsy revealed that the NMZL had transformed into a diffuse large B-cell lymphoma. This patient died after 2 years from the initial diagnosis due to lymphoma progression. Cases of CD5-positive NMZL are rare; thus, it is difficult to study the clinical implications of CD5 expression in this disease. Here we describe the current understanding of CD5 expression in NMZL.

We disclose that fluoroalkanesulfinate salts ((RFSO2)nM) such as the Langlois reagent, CF3SO2Na, serve as dual fluoroalkyl (RF) and sulfur dioxide (SO2) sources by the action of photoredox catalysis. An operationally simple strategy for the vicinal installation of RF and SO2 groups onto unsaturated carbon-carbon bonds, i.e., fluoroalkyl-sulfonylation, has been developed. In particular, the present photocatalytic trifluoromethyl-sulfonylation can be applied to aromatic alkynes in addition to aliphatic and aromatic alkenes bearing various functional groups.

We disclose that fluoroalkanesulfinate salts ((R

Highlights • Almost 12 % of participants were both socially isolated and homebound. • Participants with co-existing social isolation and homebound status were less likely to regularly utilize outpatient and home medical care. • Participants with co-existing social isolation and homebound status had higher expenditure per day for outpatient and home medical care during the year before death. • Co-existing social isolation and homebound status may eventually lead to worsening health problems that require more intensive treatment., Objective To examine whether co-existing social isolation and homebound status influence medical care utilization and expenditure in older adults. Methods Postal surveys on social isolation and homebound status were performed on older adults aged ≥65 years residing in a Japanese suburban city. Information on medical care utilization and expenditure was obtained from insurance claims data. These outcomes were examined over a three-year period (December 2008 to November 2011) for all participants (Analysis I, n = 1386) and during the last year of life for mortality cases (Analysis II, n = 107). A two-part model was used to analyze the influence of social isolation and homebound status on medical care utilization (first model: logistic regression model) and its related expenditure (second model: generalized linear model). Results Almost 12 % of participants were both socially isolated and homebound. Analysis I showed that these participants were significantly less likely to use outpatient and home medical care than participants with neither characteristic (odds ratio: 0.536, 95 % confidence interval: 0.303−0.948). However, Analysis II showed that participants with both characteristics had significantly higher daily outpatient and home medical expenditure in the year before death than participants with neither characteristic (risk ratio: 2.155, 95 % confidence interval: 1.338−3.470). Discussion Older adults who are both socially isolated and homebound are less likely to regularly utilize medical care, which may eventually lead to serious health problems that require more intensive treatment. Measures are needed to encourage the appropriate use of medical care in these individuals to effectively manage any existing conditions.

Oral candidiasis infection is generally treated with antifungal agents. However, it often requires long-term treatment, and epithelial dysplasia may persist even after the infection has been resolved depending on the case. Malignant transformation has been reported in long-term cases involving chronic inflammation, and surgical excision should be performed as the treatment of choice when the treatment period is prolonged. This report describes a case of maxillary gingival carcinoma caused by chronic inflammation related to oral candidiasis. The patient was an 85-year-old man who was admitted to our hospital with maxillary gingival pain. Cytology and biopsy revealed oral candidiasis and squamous cell carcinoma(cT1N0M0, Stage Ⅰ). He underwent partial maxillectomy. Post-operative recovery was uneventful, and there was no sign of recurrence or metastasis at the 1-year follow-up.

Aim The health benefits of paid employment in late life are understood, but they might vary according to work motives. We examined the health effects of employment among older adults, focusing on motivation. Methods We carried out a 2-year longitudinal survey from 2013 (baseline) to 2015 (follow up). Among 7608 older adults, the analysis included 1069 who completed both surveys and were employed at baseline. Work motives were assessed using a questionnaire. Participants were assigned to groups based on their responses: (i) financial reasons; (ii) motivation other than financial reasons; and (iii) both financial and non-financial reasons. Self-rated health, mental health and higher-level functional capacity were evaluated as health outcomes. Results There were group differences in baseline demographic variables and health status; those with financial reasons had lower socioeconomic status and worse mental health. Multivariable logistic regression analysis showed that compared with older workers with non-financial reasons, those with financial reasons were more likely to decline in self-rated health (OR 1.42; 95% CI 1.00-2.03) and higher-level functional capacity (OR 1.55; 95% CI 1.16-2.07), which was independent of potential covariates, including socioeconomic status. However, no differences were evident between those with only non-financial reasons and those having both financial and non-financial reasons. Conclusions We found that the participants who worked only for financial rewards had reduced health benefits through working in old age. A prolonged working life among older workers can contribute to maintaining health and can be enhanced by non-financial reasons, such as finding meaning in life and social contact. Geriatr Gerontol Int 2020; 20: 745-751.

Information is lacking about the selection criteria for silicone resilient denture liners applied as a matrix material for attachments on overdentures.The purpose of this in vitro study was to investigate the mechanical properties of silicone resilient denture liners and their influence on the initial retention force of overdenture attachments and the reduction in retention force over time.Nine types of silicone resilient denture liner were injected and fixed to the matrix section of an experimental denture base. They were then fitted to an epoxy resin model that simulated the residual ridge with a patrix ball attachment (n=10). The retention force of the denture was measured with a digital force gauge, and the maximum force of traction (N) was regarded as the initial retention force. The retention force reduction (N) after repeated insertion and removal (n=5) was calculated by subtracting the retention force after 3348 cycles (3-year simulated insertion and removal) from the initial retention force. The intaglio of the matrix was observed with a scanning electron microscope (SEM) before and after the 3348 cycles. Four mechanical properties (hardness, strain-in-compression, tensile strength, and arithmetic mean roughness) of the resilient denture liners were measured. One-way ANOVA of the initial retention force of each lining material was performed, followed by the Scheffe test (α=.05). Pearson correlation analysis was used (α=.05) to analyze correlations of the initial retention force with the retention force reduction after insertion and removal and the mechanical properties of each material. Multiple regression analysis with the stepwise method extracted the initial retention force and the retention force reduction as dependent variables, and the resilient denture liner mechanical properties as explanatory variables (α=.05).The initial retention force of the resilient denture liners was 1.3 to 5.4 N. Multiple comparisons showed significant differences in some groups (P.05). The retention force reduction of the resilient denture liners was 0.2 to 1.9 N. Multiple regression analysis with the stepwise method extracted hardness and strain-in-compression as explanatory variables for the initial retention force and the retention force reduction.Within the limitations of this in vitro study, hardness was found to influence the initial retention force of the overdenture, and strain-in-compression influenced the retention force reduction in the 3-year simulation.

Fusion genes involving MEF2D have recently been identified in precursor B-cell acute lymphoblastic leukemia, mutually exclusive of the common risk stratifying genetic abnormalities, although their true incidence and associated clinical characteristics remain unknown. We identified 16 cases of acute lymphoblastic leukemia and 1 of lymphoma harboring MEF2D fusions, including MEF2D-BCL9 (n=10), MEF2D-HNRNPUL1 (n=6), and one novel MEF2D-HNRNPH1 fusion. The incidence of MEF2D fusions overall was 2.4% among consecutive precursor B-cell acute lymphoblastic leukemia patients enrolled onto a single clinical trial. They frequently showed a cytoplasmic μ chain-positive pre-B immunophenotype, and often expressed an aberrant CD5 antigen. Besides up- and down-regulation of HDAC9 and MEF2C, elevated GATA3 expression was also a characteristic feature of MEF2D fusion-positive patients. Mutations of PHF6, recurrent in T-cell acute lymphoblastic leukemia, also showed an unexpectedly high frequency (50%) in these patients. MEF2D fusion-positive patients were older (median age 9 years) with elevated WBC counts (median: 27,300/ml) at presentation and, as a result, were mostly classified as NCI high risk. Although they responded well to steroid treatment, MEF2D fusion-positive patients showed a significantly worse outcome, with 53.3% relapse and subsequent death. Stem cell transplantation was ineffective as salvage therapy. Interestingly, relapse was frequently associated with the presence of CDKN2A/CDKN2B gene deletions. Our observations indicate that MEF2D fusions comprise a distinct subgroup of precursor B-cell acute lymphoblastic leukemia with a characteristic immunophenotype and gene expression signature, associated with distinct clinical features.

Well-defined 9,10-bis(di(p-tert-butylphenyl)amino)anthracene serves as a photocatalyst for radical fluoroalkylation under visible light irradiation. The diarylamine (Donor)–anthracene (π conjugated system)–diarylamine (Donor) scaffolds are easily accessed by typical palladium-catalyzed cross-coupling protocols of the corresponding halogenated anthracenes with various lithium diarylamides. The anthracene-based photocatalyst exhibits high reducing power, leading to generation of versatile fluoroalkyl radicals such as tri- and difluoroethyl and tri- and difluoromethyl radicals from the corresponding electron-accepting precursors. Catalyst design strongly influences the absorption capability of visible light and stability toward redox stimuli. The detailed mechanistic studies on the metal-free photocatalytic amino-trifluoroethylation of styrene with diphenyl(2,2,2-trifluoroethyl)sulfonium trifluoromethanesulfonate suggest that the reaction proceeds via catalytic radical processes rather than radical chain pro...

Background:Social isolation and homebound statuses are possible risk factors for increased mortality among older adults. However, no study has addressed the impact of accumulation of these two factors on mortality. The aim of this study was to examine whether such accumulation increased the risk of all-cause mortality.Methods:The analyzed sample was drawn from a mail survey of 1,023 older adults without instrumental activities of daily living disability. Participants were classified into four groups according to the frequency of both face-to-face and non-face-to-face interactions with others (social isolation and non-social isolation) and the frequency of going outdoors (homebound and non-homebound). Social isolation and homebound statuses were defined as having a social interaction less than once a week and going outdoors either every few days or less, respectively. All-cause mortality information during a six-year follow-up was obtained.Results:In total, 78 (7.6%) participants were both socially isolated and homebound. During the follow-up period, 65 participants died, with an overall mortality rate of 10.6 per 1000 person-years. Cox proportional hazards regression analyses demonstrated that older adults who were socially isolated and homebound showed a significantly higher risk of subsequent all-cause mortality compared with healthy adults who were neither socially isolated nor homebound, independent of potential covariates (aHR, 2.19; 95% CI: 1.04–4.63).Conclusion:Our results suggest that the co-existence of social isolation and homebound statuses may synergistically increase risk of mortality. Both active and socially integrated lifestyle in later life might play a major role in maintaining a healthy status.

Aim Identifying factors that influence participation in social group activities in older adults might be helpful in promoting social participation in this population. We examined factors related to new or continuous participation in social group activities according to group type. Methods We carried out a community-based, longitudinal study with a 2-year follow-up period. Of 7608 older adults aged ≥65 years, 3380 completed the follow-up survey and were included in the analysis. We examined private group (hobbies, sports and volunteering; PrG) and public group (neighborhood associations and senior citizen clubs; PuG) activity. Results For PrG, 39.6% of the participants were engaged at baseline, 25.5% initiated participation and 9.5% withdrew during the study period. For PuG, 20.8% of the participants were engaged at baseline, 10.8% initiated participation and 31.5% withdrew during the study period. Logistic regression analysis showed mental health, self-rated health, employment, relationships with neighbors, subjective economic status, educational attainment and participation in PuG were related to new participation in PrG. Mental health, employment and relationships with neighbors were significantly related to continuous participation. For PuG, mental health, sex and relationships with neighbors were significantly related to new participation, whereas sex, relationships with neighbors and educational attainment were related to continuous participation. Conclusions The rate of new and continuous participation in PrG was higher than that in PuG, and different related factors were identified as existing between social group types. Geriatr Gerontol Int 2018; 18: 1259-1266.

To distinguish between first wheeze and asthma in early childhood, we investigated respiratory viruses and cytokine/chemokine profiles among patients with first wheeze and established asthma.We enrolled children with acute exacerbations of wheezing (17 first wheeze and 32 asthma) and 11 controls (no wheezing) aged between 10 months and 6 years. Nasal aspirates were obtained, and virus detection was performed with antigenic assay kits and/or RT-PCR. Serum 27 cytokines/chemokines were assayed by a multi-cytokine detection system.Rhinovirus and respiratory syncytial (RS) virus were dominant in acute exacerbations of asthma. However, many types of viruses were isolated in first wheeze. Serum IL-8 and IL-12 values were significantly higher in first wheeze than in acute asthma or the controls. IL-5 and IP-10 levels in acute asthma and first wheeze cases were higher than in the controls. Both of them were significantly higher in cases of acute asthma than in convalescence stage of asthma cases. Only IP-10 was significantly higher in first wheeze than in convalescence stage of first wheeze cases.Different profiles in virus detection and production of IL-8 and IL-12 might distinguish between first wheeze and childhood asthma.

Summary Radical tri- and difluoromethylation (fluoromethylation) by photoredox catalysis has emerged as a new synthetic methodology over the past several years. In particular, the strategy is useful for the introduction of a fluoromethyl group (CF 2 X, X = F or H) and a different functional group across a carbon-carbon double bond via a single operation. Step-economical synthesis of diverse organofluorine compounds bearing a C(sp 3 )–CF 2 X bond has been achieved. In this review, the discussion focuses on recent representative examples of photoredox-catalyzed fluoromethylative difunctionalization of alkenes through redox-neutral processes. Close attention is paid to the choice of the fluoromethylating reagent and the photocatalyst. The basic concept, reaction design, and the prospects for this research area are also discussed.

Orbital blowout fractures frequently occur along the floor or medial aspect of the orbital wall, which are the two thinnest areas of the bony orbit. True trapdoor injuries of the orbit are less common and rarely involve an isolated medial wall injury. In addition, they usually occur in pediatric patients. An isolated medial wall trapdoor type blowout fracture in adults is extremely rare. Here, we report an isolated medial wall trapdoor type blowout fracture in a 44-year-old woman with restricted ocular mobility due to medial rectus muscle entrapment, the so-called ‘missing rectus muscle’. A prompt diagnosis and early surgical intervention achieved a satisfactory clinical outcome.

Introduction: Myeloid/Natural killer (NK) cell precursor acute leukemia (MNKPL) is a rare hematologic malignancy prevalent in East Asia. MNKPL is characterized by extramedullary involvement, immature lymphoblastoid morphology without myeloperoxidase (MPO) reactivity, the CD7+/CD33+/CD34+/CD56+/HLA−DR+ phenotype. MNKPL is classified as mixed phenotype acute leukemia, and not otherwise specified rare types (MPAL NOS rare types) in WHO classification. However, its characteristic clinical feature and undetermined genetic feature suggests that MNPKL leaves open the possibility of a new independent disease concept. Here, we report clinical features and genetic alterations in patients with MNKPL. Methods: The Leukemia and Lymphoma Committee of the Japanese Society of Pediatric Hematology and Oncology (JSPHO) sent out questionnaires to 110 JSPHO affiliated hospitals and collected cases of MNPKL diagnosed during the period 2000-2013. Besides, the cases published as literature were recruited. The data of clinical features, cell surface antigen profiling, overall survival (OS), and event-free survival (EFS) defined as relapse or death were also collected as a secondary survey. The protocol of this retrospective study was approved by the review boards of JSPHO and Ehime Prefectural Central Hospital. Comprehensive genetic analysis including 13 whole-exome sequences (WES), 2 target sequence, 6 RNA sequence (RNA-seq), and 8 DNA methylation analysis was performed. We also performed single-cell RNA-seq using 1 sample of MNKPL patients and a normal bone marrow sample as the reference. The research protocol was approved by the review board of TMDU. Results: Sixteen children or young adults (< 39 years old) and 2 older adults with MNKPL were identified. The median age of MNKPL patients was 11 (0.5-75) years old. There are 12 males and 6 females. The extramedullary involvement was observed in 7 patients. Complete remission after induction therapy was achieved in 8/14 (57%) patients treated with acute myeloid leukemia (AML) type chemotherapy and 2/4 (50%) patients treated with acute lymphoblastic leukemia (ALL)/non-Hodgkin lymphoma type chemotherapy, respectively. Fifteen patients underwent hematopoietic cell transplantation (HCT). The median follow-up period was 3.8 (0.1-16.0) years. 5-year OS and 5-year EFS was 49.5% and 40.7%, respectively. In genetic analysis, median 388 somatic mutations in MNKPL were identified by WES. The recurrent mutations were observed in NOTCH1 (n=5), MAML3 (n=4), NRAS, MAP3K4, RECQL4, CREBBP, ASXL2, and KMT2D (n=3, respectively), and MAML2, MAP3K1, FLT3, CARD11, MSH4, FANCI, WT1, ZNF384, and ERG (n=2, respectively). The distinct expression pattern, higher expression of RUNX3 and NOTCH1, and lower expression of BCL11B were identified in MNKPL samples which were compared to MPAL, AML, and T cell ALL in RNA-seq. The distinct methylation profile, hypomethylation of RUNX3 regulatory region, and hypermethylation of BCL11B regulatory region were identified in DNA methylation analysis. Single-cell RNA-seq analysis also showed distinct 4 subsets of MNKPL. Discussion and Conclusions: NK cells are the founding member of a family of innate lymphoid cells (ILC). Genetic abnormality of NOTCH1 pathway is a hallmark of MNPKL. RUNX3 is required for NK cell survival and proliferation in response to IL-15 signaling. RUNX3 high expression and hypomethylation of RUNX3 regulatory region also characterize MNKPL. Currently, MNKPL is classified as MPAL NOS, our genetic analysis revealed that MNKPL is a distinct group from MPAL. The prognosis of MNKPL was not satisfactory even though HCT was performed. The development of new therapeutic approaches based on these genetic analyses is highly expected. Disclosures Saito: Toshiba Corporation: Research Funding. Nakazawa:Toshiba Corporation: Research Funding.

We have developed novel oxytrifluoromethylation of aryl-substituted allenes by photoredox catalysis. The present photocatalytic system allows direct and stereoselective synthesis of 2-CF3-allyl acetates bearing tetrasubstituted CF3-alkene scaffolds in a single operation. The obtained CF3-allyl acetates can be applied to further functionalization as CF3-containing building blocks.

Regioselective amino-difluoromethylation of aromatic alkenes via C(sp3)–CF2H and C(sp3)–N bond formation with the CC moiety has been achieved in a single operation by visible-light photoredox catalysis. The combination of a shelf-stable and easy-to-handle sulfonium salt, S-difluoromethyl-S-di(p-xylyl)sulfonium tetrafluoroborate, and perylene catalysis is the key to the successful transformation. Furthermore, this noble metal-free protocol allows for the photocatalytic trifluoromethylation of alkenes.

Little is known about the association between bacterial infections and exacerbations of bronchial asthma.To elucidate the effect of bacterial infections on bronchial asthma, we examined pharyngeal bacterial colonization, duration of wheezing, and serum levels of cytokines and chemokines during acute exacerbations of asthma in children.Potential bacterial pathogens were investigated in pharyngeal samples and viruses obtained from nasal secretions of 111 children who were outpatients and/or in patients with acute exacerbations of asthma (mean/median age: 2.8/2.6, respectively). We also measured serum levels of 27 different cytokines/chemokines.Pharyngeal bacterial cultures were positive in 110 of 111 children. The 3 major bacterial pathogens were Streptococcus pneumoniae (29.7%), Moraxella catarrhalis (11.7%), and Haemophilus influenzae (10.8%). M. catarrhalis was detected more frequently in patients with pneumonia. Furthermore, patients with S. pneumoniae colonization had significantly shorter wheezing episodes than those without it. In contrast, the duration of wheezing did not differ significantly among cases with other bacteria such as M. catarrhalis and H. influenzae. Furthermore, the length of wheezing episode in patients with S. pneumoniae colonization showed significant inverse correlation with peripheral white blood cell count, neutrophil count, and C-reactive protein, while there was no significant correlation between duration of wheezing and these 3 parameters among patients with M. catarrhalis or H. influenza. Among the 27 cytokines/chemokines, only serum tumor necrosis factor (TNF)-α was significantly lower in patients with S. pneumoniae colonization than in those without it.These results suggested that pharyngeal S. pneumoniae colonization plays a suppressive role on the pathophysiology during acute exacerbations of asthma.

If the alveolar bone height of patients requiring dental implants in the maxillary molar region is inadequate, it is difficult to achieve satisfactory outcomes using existing bone graft materials. We previously reported the possible utility of bacterial cellulose (BC) as a new dental treatment material. BC has a high absorptive capacity, good mechanical strength, and good volume retention. BC loaded with bone morphogenetic protein-2 (BMP-2) might allow effective alveolar bone augmentation. We created critical frontal bone defect models in 12 male Japanese white rabbits and divided them into four groups: sham, BC (BC grafting only), BMP-2 (treated with BMP-2 solution only), and BC+BMP-2 (grafted with BC loaded with BMP-2). Newly formed bone volume was calculated via hematoxylin-eosin staining evaluation. The proliferating cell nuclear antigen and osteocalcin levels were determined by the immunohistochemical staining analysis. All measured indices of the BC+BMP-2 group were significantly superior to those of the other groups (all p &lt, 0.05). BC maintained the graft space and released BMP-2 in a sustained manner, promoting optimal bone formation. The BC+BMP-2 combination enhanced bone regeneration and shows promise as a useful means of clinical pre-dental implant bone augmentation in the maxillary sinus.

Retrobulbar emphysema is a rare condition compared to the more common orbital emphysema. It is often associated with medial orbital wall fracture with rupture of the periosteum. In some severe patients, retrobulbar emphysema can increase the intraorbital pressure and lead to orbital compartment syndrome. Less extreme patients require only conservative treatment with careful observation. There is still no standard protocol for the management of orbital emphysema in general or specifically for retrobulbar emphysema. Visual acuity is the most widely used indicator to determine whether surgical intervention is needed. The patient presented here suffered from large retrobulbar intraconal emphysema and exophthalmos without visual loss after head trauma and nose blowing. He was observed closely without surgical intervention. After the emphysema had resolved, the patient's medial orbital wall defect was reconstructed using unsintered hydroxyapatite particles/poly L-lactide via the transcaruncular approach. The postoperative course has been uneventful with more than 1 year of follow-up to date.

The use of bortezomib in the clinic has significantly improved outcomes for patients with multiple myeloma (MM), even those harboring high-risk cytogenetic abnormalities or those classified in the high-risk category according to the International Staging System (ISS). In this study, we analyzed the association between immunophenotyping on myeloma cells and the clinical outcomes of patients who received bortezomib-based regimens as first-line therapy. Immunophenotypic analysis before bortezomib therapy was performed by flow cytometry, and whether the immunophenotyping results influenced the clinical outcomes of the patients was investigated. Seventy-four newly diagnosed patients with MM were included in this study. We found that the expression of MPC-1 significantly predicted the time to next therapy (TNT), with a longer TNT in the MPC-1 positive group (p = 0.005), whereas it did not affect overall survival (OS; p = 0.773). In addition, we found that CD45-positivity was associated with shorter TNT (p = 0.0432). Following ISS assessment at treatment initiation, patients who were classified as stage I showed a slightly longer OS compared to those at stage II or III; however, these results were not significant (p = 0.0987). Furthermore, multivariate analysis revealed the prognostic significance of MPC-1 expression, as MPC-1-negativity was associated with a worse TNT. The combination of MPC-1 and CD45 status more sensibly predicted the TNT for bortezomib therapy. Our results demonstrate the clinical importance of immunophenotyping on myeloma cells to determine patient prognoses in this era of novel therapeutic agents.

Oral leukoplakia is the most common premalignant or potentially malignant lesion in the oral mucosa. This retrospective study examined 67 lesions from 62 patients with clinical diagnoses of oral leukoplakia who underwent surgical excision in our department from 2015 to 2017. The patients comprised 22 men and 40 women. The most common location of the lesion was the lower gingiva, followed by the tongue, upper gingiva, buccal mucosa, palate, and lip. The most common clinical type was the white-spotted, followed by erythroleukoplakia, hillock, and verrucous types. Histopathologically, 16 lesions were oral intraepithelial neoplasia, whereas five were squamous cell carcinoma. The data identified several characteristics of oral leukoplakia that predict a high risk of malignant transformation and require aggressive surgical resection.

The pedicled pectoralis major myocutaneous(PMMC)flap, used for the reconstruction of surgical defects in advanced oral cancer resection, is versatile and can be obtained without a highly-invasive procedure. However, flap utility is limited by an unstable blood supply and the relatively high rate of partial necrosis of the skin island. Thus, the use of microvascularized free flaps has become more common in patients requiring oral-maxillofacial reconstruction. Detailed angiographic studies revealed the 3-dimensional vascular anatomy of the PMMC flap. This allowed us to obtain a modified, heart-shaped flap with a skin island that includes the intramuscular vascular networks between the pectoral branches of the thoracoacromial vessels and the intercostal perforators of the internal mammary vessels, thus ensuring a sufficient blood supply and stable survival of the flap. We have used this technique since 2015 to treat 7 patients with locally advanced or recurrent(salvage)oralcancer. None developed critical flap problems, and survival of the total skin island was successfully obtained in all cases. Transfer of the heart-shaped PMMC, including the multiple intercostal perforators from the internal mammary vessels, may contribute to a stable blood supply of the skin island and therefore can be effective for advanced oral cancer reconstruction.

Purpose: We investigated the feasibility of isolated medial orbital wall fracture reconstruction using an unsintered hydroxyapatite particles/poly L-lactide (u-HA/PLLA) sheet implant with the assis...

Fluorinated groups are prevalent in pharmaceutical and agrochemical compounds as they significantly influence the absorption, distribution, metabolism, and excretion properties of a molecule in biological systems. Photocatalytic radical processes enable the facile introduction of fluorinated groups into various organic skeletons. This chapter presents recent representative works and standard procedures to achieve such processes.

The prognosis of paediatric acute myeloid leukaemia (AML) with primary induction failure (PIF) is extremely poor, and effective treatment strategies have not been established. We investigated the clinical and biological features of paediatric AML patients with PIF registered to the Japanese Paediatric Leukaemia/Lymphoma Study Group AML-05 study. The 3-year overall survival rate of the 41 PIF patients was 19.0%. High leucocyte count, M7 morphology, and unfavourable genetic aberrations, such as FLT3-internal tandem duplication, NUP98-NSD1 and high MECOM or PRDM16 expression, were risk factors for PIF. More effective treatment strategies based on leukaemia biology need to be urgently explored.

Studies using Fanconi anaemia (FA) mutant mouse models suggested that the combination of a defective FA pathway and aldehyde dehydrogenase-2 (ALDH2) dysfunction could provoke bone marrow failure, leukaemia and developmental defects, and that both maternal and fetal aldehyde detoxification are crucial to protect the developing embryo from DNA damage. We studied the ALDH2 genotypes of 35 Japanese FA patients and their mothers. We found that a normal maternal ALDH2 allele was not essential for fetal development of ALDH2-deficient patients, and none of the post-natal clinical parameters were clearly affected by the maternal ALDH2 genotype in these patients.

Simple synthesis of CF3- and CF2H-spiroethers from aryl-fused cycloalkenylalkanols by photoredox catalysis has been developed. Modification of the fluoromethylating reagents and the photoredox catalysts leads to both CF3- and CF2H-spiroetherification. The present photocatalytic system allows us to access a variety of new anti-fluoromethylated spiroethers in a highly selective manner.

Combination of organotrifluoroborates and visible-light-driven photoredox catalysis, both of which have attracted the attention of synthetic chemists, marks a new phase in the field of organic radical chemistry. We have developed photoredox-catalyzed radical reactions with organotrifluoroborates, which turn out to serve not only as a source of organic radicals but also as radical acceptors. The first part of this Perspective deals with the generation of organic radicals from organotrifluoroborates, and the latter part describes addition of the CF3 radical to alkenyltrifluoroborates. The good chemistry between organoborates and photoredox catalysis and its future will be discussed.

Aim Decreased frequency of going outside the home and being socially isolated are regarded as predictors of poor health. The object of the present study was to clarify whether these factors have synergistic or independent impacts on future functional decline. Methods We examined a prospective cohort of 2427 community-dwelling persons, aged ≥65 years, who responded to the baseline mail survey in Wako City, in 2008. Participants were asked about the frequency of going outside the home, social isolation status (having contact less than once a week with anyone outside household), functional capacity (Tokyo Metropolitan Institute of Gerontology-Index of Competence), age, sex, annual income, self-rated health, depressive mood and mobility. Results Of 1575 persons (72.1%) who completely responded to the follow-up survey (T2) in 2012, we defined the groups as follows: group 1, not isolated and going outside the home every day (n = 897); group 2, not isolated and going outside the home less than every day (n = 311); group 3, isolated and going outside the home every day (n = 224); and group 4, isolated and going outside the home less than every day (n = 143). Multiple logistic regression analyses showed that the variables identifying group 3 for men and group 2 for women with reference to group 1 were predictors of subsequent functional decline even after adjustment for confounders (odds ratios 2.01, 1.63; 95% CI 1.20–3.38, 1.03–2.56, respectively). Conclusion Social isolation regardless of going outside the home every day for men and going outside the home less than every day regardless of being not socially isolated for women might predict functional decline. Geriatr Gerontol Int 2016; ●●: ●●–●●.

We have developed a novel and simple protocol for the direct incorporation of a difluoromethyl (CF2H) group into alkenes by visible‐light‐driven photoredox catalysis. The use of fac‐[Ir(ppy)3] (ppy=2‐pyridylphenyl) photocatalyst and shelf‐stable Hu's reagent, N‐tosyl‐S‐difluoromethyl‐S‐phenylsulfoximine, as a CF2H source is the key to success. The well‐designed photoredox system achieves synthesis of not only β‐CF2H‐substituted alcohols but also ethers and an ester from alkenes through solvolytic processes. The present method allows a single‐step and regioselective formation of C(sp3)–CF2H and C(sp3)−O bonds from C=C moiety in alkenes, such as hydroxydifluoromethylation, regardless of terminal or internal alkenes. Moreover, this methodology tolerates a variety of functional groups.